The continuous loss of lung tissue as a result of age, and more importantly smoking, only manifests as symptoms when the degree of parenchyma destruction limits metabolic rate by frustrating gas exchange. There is currently no clear diagnostic methodology by which early detection of tissue loss can be assessed. We propose to develop a new metric that can quantitatively measure lung tissue microstructure in smokers. This study could be useful for observing the onset of early emphysema and validating the safety and efficacy of emphysema interventions. Hyperpolarized xenon (HyXe) MRI was recently demonstrated by our collaborative partnership to provide exquisitely sensitive measurements of regional alveolar lung surface area on the few micron scale. By using the xenon chemical shift to distinguish xenon dissolved in tissue from xenon in the gaseous phase, we observed the temporal increase in phase exchange to depend on the square root of the exchange time. The ratio of the dissolved signal to the gas signal is proportional to the parenchyma partition coefficient and the average surface-to-volume ratio. The time to saturation reveals the parenchyma thickness (squared) scaled by the tissue diffusion constant. We propose measurements of lung surface area in smokers correlated with pack-years. In Phase 1 we will measure 20 subjects with smoking histories greater than 20 pack-years and 10 age and gender matched healthy adults. Data will be analyzed to determine average lung surface area correlates in males and females. In Phase 2 we will expand the study statistics to include more smokers, and remeasure the original subjects to determine tissue loss with time in a longitudinal study. [unreadable] [unreadable] [unreadable]